DESCRIPTION: The candidate indicates that Cryptococcus neoformans causes life threatening infections in 6-8% of patients with AIDS, that C. neoformans has a polysaccharide capsule which is a determinant of virulence and is antiphagocytic, and that capsule binding antibodies are potent opsonins which have been shown to prolong survival in murine models following intravenous inoculation of the fungus. However, the fungus enters its host through the respiratory tree and little is known about the role of antibody immunity in pulmonary infections. This information is increasingly important given the ongoing development of a conjugate vaccine which elicits antibody formation. Preliminary data indicated that systemic antibody protects against a primary pulmonary C. neoformans infection. The overall theme of this application is to study the mechanism of the antibody mediated protection in pulmonary infections. Four aims are proposed. Aim 1 will determine the efficacy of antibody in modifying the course of pulmonary infection. Aim 2 will determine the mechanism of serum antibody protection in the lung. Aim 3 will explore the contribution of cytokine expression to antibody mediated protection in the lung. Aim 4 will determine the mechanisms of extrapulmonary dissemination of C. neoformans.